Intraocular pressure (IOP) in the eye is maintained by a continuous flow of aqueous humor produced by the ciliary body. Excess fluid flows out of the eye through the trabecular meshwork. If the outflow is blocked, aqueous humor builds up inside the eye leading to increased IOP and ocular hypertension. The ocular hypertension can damage the optic nerve, resulting in an optic neuropathy and irreversibly impaired vision. This condition, known as glaucoma, affects more than 60 million people worldwide and is the second leading cause of blindness. Increased IOP is the key modifiable risk factor for glaucoma.
Conventional treatments for ocular hypertensive and glaucoma patients include ocular surgery and topical eye drop instillation. These treatment modalities have drawbacks. For example, not all patients are candidates for ocular surgery. Additionally, although topical eye drops are generally considered to be effective, patients' long-term compliance with instillation schedules is a major issue. Ocular hypertension and glaucoma cannot be well controlled if patients do not adhere to the proper topical eye drop instillation schedule.
Topical eye drops contain drugs for controlling IOP which typically act by reducing fluid production by the eye, increasing fluid outflow, or by both mechanisms. Prostaglandin analogues, e.g., latanoprost, are potent drugs which can reduce IOP by increasing aqueous outflow through the uveoscleral pathway.
Typically, only 5% of free drug applied to the corneal epithelium via eye drops successfully penetrates through the cornea. As a result, the amount of drug reaching the aqueous humor often falls below the therapeutically effective concentration. This necessitates repeated administration. Additionally, a substantial portion of the drug can enter the circulation via the conjunctival sac, causing undesirable systemic side effects.
As an alternative to topical eye drops, subconjunctival injection of a sustained release IOP-reducing drug can be used to deliver drugs directly to the site of action. Such a delivery modality solves the problems of patient non-compliance with instillation schedules and inefficient drug transport across the cornea.
The need exists for a stable drug formulation for subconjunctival injection requiring a minimal frequency of administration for long-term stable control of IOP.